Journal
COMMUNICATIONS BIOLOGY
Volume 3, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s42003-020-01362-w
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Funding
- Canadian Cancer Society Research Institute
- Canadian Breast Cancer Foundation
- Joseph and Wolf Lebovic Fellowship Program
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Cancer immunotherapies using monoclonal antibodies to block inhibitory checkpoints are showing durable remissions in many types of cancer patients, although the majority of breast cancer patients acquire little benefit. Human melanoma and lung cancer patient studies suggest that immune checkpoint inhibitors are often potent in patients that already have intratumoral T cell infiltrate; although it remains unknown what types of interventions can result in an intratumoral T cell infiltrate in breast cancer. Using non-T cell-inflamed mammary tumors, we assessed what biological processes and downstream inflammation can overcome the barriers to spontaneous T cell priming. Here we show a specific type of combination therapy, consisting of oncolytic virus and chemotherapy, activates necroptosis and limits tumor growth in autochthonous tumors. Combination therapy activates proinflammatory cytokines; intratumoral influx of myeloid cells and cytotoxic T cell infiltrate in locally treated and distant autochthonous tumors to render them susceptible to immune checkpoint inhibitors. Workenhe et al. show in mice that a combination of oncolytic HSV-1 virus and Mitomycin-C activates an inflammatory response, through necroptosis induction, that renders tumours susceptible to immune checkpoint inhibitors. These findings informs on the potential role of necroptosis in immunotherapy approaches.
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